AUTHOR=Herrera Maria I. , Udovin Lucas D. , Kobiec Tamara , Toro-Urrego Nicolas , Kusnier Carlos F. , Kölliker-Frers Rodolfo A. , Luaces Juan P. , Otero-Losada Matilde , Capani Francisco TITLE=Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=16 YEAR=2022 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2022.953157 DOI=10.3389/fnbeh.2022.953157 ISSN=1662-5153 ABSTRACT=

Impaired gas exchange close to labor causes perinatal asphyxia (PA), a neurodevelopmental impairment factor. Palmitoylethanolamide (PEA) proved neuroprotective in experimental brain injury and neurodegeneration models. This study aimed to evaluate PEA effects on the immature-brain, i.e., early neuroprotection by PEA in an experimental PA paradigm. Newborn rats were placed in a 37°C water bath for 19 min to induce PA. PEA 10 mg/kg, s.c., was administered within the first hour of life. Neurobehavioral responses were assessed from postnatal day 1 (P1) to postnatal day 21 (P21), recording the day of appearance of several reflexes and neurological signs. Hippocampal CA1 area ultrastructure was examined using electron microscopy. Microtubule-associated protein 2 (MAP-2), phosphorylated high and medium molecular weight neurofilaments (pNF H/M), and glial fibrillary acidic protein (GFAP) were assessed using immunohistochemistry and Western blot at P21. Over the first 3 weeks of life, PA rats showed late gait, negative geotaxis and eye-opening onset, and delayed appearance of air-righting, auditory startle, sensory eyelid, forelimb placing, and grasp reflexes. On P21, the hippocampal CA1 area showed signs of neuronal degeneration and MAP-2 deficit. PEA treatment reduced PA-induced hippocampal damage and normalized the time of appearance of gait, air-righting, placing, and grasp reflexes. The outcome of this study might prove useful in designing intervention strategies to reduce early neurodevelopmental delay following PA.